Daily Endocrinology Research Analysis
Three papers stand out today in endocrinology: a large population-based study from the Middle East reveals under-recognized obesity when applying ethnicity-specific thresholds; a real-world assessment shows that screening for primary aldosteronism in primary care using ARR is feasible and accurate; and a meta-analysis indicates that so-called non-functioning adrenal incidentalomas carry measurable metabolic risks and can become functional over time.
Summary
Three papers stand out today in endocrinology: a large population-based study from the Middle East reveals under-recognized obesity when applying ethnicity-specific thresholds; a real-world assessment shows that screening for primary aldosteronism in primary care using ARR is feasible and accurate; and a meta-analysis indicates that so-called non-functioning adrenal incidentalomas carry measurable metabolic risks and can become functional over time.
Research Themes
- Obesity epidemiology and diagnostic thresholds
- Primary aldosteronism screening in primary care
- Metabolic risks and progression of non-functioning adrenal incidentalomas
Selected Articles
1. Prevalence of overweight and obesity in adults from the Middle East: A large-scale population-based study.
In a cross-sectional analysis of 440,590 adults in Dubai, 63.4% were living with overweight or obesity. Applying ethnicity-specific thresholds raised estimated obesity prevalence from 28.0% to 35.8%, with particularly high rates among UAE national women aged ≥40. The study highlights how standard WHO cut points may under-detect clinically actionable obesity in Southeast Asian populations.
Impact: This is among the largest direct prevalence studies, operationalizing new diagnostic concepts of clinical obesity and demonstrating major underestimation when ethnicity-specific thresholds are ignored.
Clinical Implications: Adopt ethnicity-specific BMI and adiposity thresholds and consider clinical obesity criteria to identify patients eligible for therapy. Programs should target high-risk subgroups (e.g., women ≥40 years) and avoid one-size-fits-all cut points.
Key Findings
- Overall OAO prevalence was 63.4% among 440,590 adults.
- UAE nationals had higher OAO prevalence (68.3%) than SEAR nationals (59.7%) and others (63.6%).
- Women had higher obesity prevalence than men (30.4% vs 25.9%).
- Ethnicity-specific thresholds increased obesity prevalence estimates from 28.0% to 35.8%.
- About half of UAE national women ≥40 years were living with obesity; ~20% had class 2 or 3 obesity.
Methodological Strengths
- Very large, multi-centre, population-based sample (n=440,590).
- Use of both standard WHO and ethnicity-specific thresholds plus clinical obesity criteria based on ICD-10 end-organ dysfunction.
Limitations
- Cross-sectional design prevents causal inference.
- Single health system and regional focus may limit generalizability; residual confounding not fully addressed.
Future Directions: Prospective studies to link ethnicity-specific thresholds and clinical obesity criteria with incident cardiometabolic outcomes, and to validate implementation strategies across diverse health systems.
AIMS: Although there are population-level estimates of the prevalence of overweight and obesity (OAO), there are few direct epidemiological surveys of OAO prevalence at scale. MATERIALS AND METHODS: This was a cross-sectional, multi-centre, population-based study of all adults aged >18 years attending the Dubai Academic Health Corporation (DAHC) between January 2018 and August 2023. OAO was defined according to WHO standards or modified WHO cut points for individuals from WHO South-East Asian Region (SEAR) countries. Clinical obesity, defined according to new Lancet Commission diagnostic criteria, was estimated using ICD-10 codes corresponding to end-organ dysfunction. RESULTS: Of 440 590 participants, 48.5% were female, 52% were aged 19-39 years and 37.1% were UAE nationals. 63.4% of the population were living with OAO. Significantly more UAE nationals (68.3%) were living with OAO than nationals from SEAR countries (59.7%, p < 0.001) or elsewhere (63.6%, respectively, p < 0.001). Significantly more females than males were living with obesity (30.4% vs. 25.9%, p < 0.001). About a half of female UAE nationals aged ≥40 years were living with obesity, about one in five of whom had class 2 or class 3 obesity. Using modified ethnicity-specific thresholds increased the overall proportion of people living with obesity in the UAE from 28.0% to 35.8%. About a third of individuals with a body mass index ≥40 kg/m CONCLUSIONS: This is the largest epidemiological study to provide direct prevalence data on OAO at this scale in the region and one of the largest globally. Using standard WHO cut points to define OAO may severely underestimate the prevalence of clinically actionable obesity in individuals of Southeast Asian ethnicity. This first application of new diagnostic criteria of clinical obesity suggests that some individuals may be disqualified from therapy who might otherwise benefit from a patient-centric approach.
2. Is It Possible to Screen for Primary Aldosteronism Effectively in Primary Care?
Among 2,915 adults screened in primary care, 3.7% were ultimately diagnosed with primary aldosteronism. Primary care ARR correlated strongly with secondary care ARR (r=0.841) and achieved an AUC of 0.81, with a ≥30 pmol/mU cut-off yielding sensitivity comparable to secondary care. Beta-blockers increased false positives.
Impact: Demonstrates that ARR-based screening for PA can be shifted upstream to primary care without substantial loss of diagnostic performance, potentially increasing detection of a common, treatable endocrine cause of hypertension.
Clinical Implications: Implement ARR testing in primary care with attention to medication effects (e.g., beta-blockers) and use simple referral criteria to secondary care for confirmatory testing. This could reduce delayed diagnosis and improve hypertension control.
Key Findings
- Out of 2,915 adults screened, 107 (3.7%) were diagnosed with primary aldosteronism.
- Primary care ARR strongly correlated with secondary care ARR (r=0.841, p<0.001).
- Primary care ARR predicted PA with AUC 0.81 (95% CI 0.77–0.86).
- ARR ≥30 pmol/mU had sensitivity comparable to secondary care testing (91.7% vs 92.1%).
- Beta-blocker use increased risk of false positive ARR (OR 3.5, 95% CI 1.1–12.0).
Methodological Strengths
- Large real-world screened cohort over 14 years with linkage to secondary care outcomes.
- Direct performance benchmarking (correlation, ROC, concordance) between primary and secondary care ARR.
Limitations
- Retrospective design and potential referral/selection bias.
- Medication confounding (e.g., beta-blockers) and single-region setting may limit generalizability.
Future Directions: Prospective primary care implementation studies with standardized medication washout and cost-effectiveness analyses; integration into hypertension pathways to assess impact on blood pressure control and outcomes.
OBJECTIVE: Primary aldosteronism (PA) is the commonest secondary cause of hypertension but case-detection remains a challenge. Screening is usually performed in secondary care using an aldosterone:renin ratio (ARR) measurement. Here, we describe the outcomes of screening in primary care, in Oxfordshire, UK. DESIGN: Retrospective observational study. PATIENTS: Adults screened for PA in primary care services in Oxford between 2008 and 2022. MEASUREMENTS: ARR test results in primary care and outcomes of secondary care evaluation (ARR, saline infusion test, final diagnosis). Primary care and secondary care ARR tests were compared for correlation, concordance and performance in predicting PA. RESULTS: Among 2915 adults screened in primary care, 455 were referred to secondary care and 107 (3.7% of total population screened) were diagnosed with PA. Primary care ARR showed strong correlation with secondary care ARR (r = 0.841, p < 0.001). Area under the ROC curve to predict PA was 0.81 (95% CI 0.77-0.86) for primary care ARR testing. Primary care ARR cut-off of ≥ 30 pmol/mU showed comparable sensitivity (91.7% vs 92.1%, p = 0.467) to and modest concordance (Kappa 0.583, p < 0.001) with secondary care ARR. Use of beta-blockers were associated with higher risk of false positive test result (OR 3.5, 95% CI 1.1-12.0, p = 0.042). CONCLUSIONS: Screening for PA in primary care with ARR is feasible with modest concordance and comparable sensitivity to secondary care testing. Simple referral criteria and raising awareness among primary care colleagues could ensure appropriate referral to secondary care.
3. Metabolic complications and clinical outcomes of non-functioning adrenal incidentalomas: a systematic review and meta-analysis.
Across 18 studies (n=2,059), patients with NFAI managed non-surgically experienced significant increases in diabetes (RR 1.33) and lipid disorders (RR 1.22) over time, whereas hypertension and obesity did not change significantly. Approximately 4% enlarged >10 mm and 8% became functional during ~4 years; surgery improved hypertension (RR 0.67).
Impact: Challenges the assumption that NFAIs are metabolically inert and quantifies risks of progression (growth and functional change), informing surveillance and management strategies.
Clinical Implications: Consider structured metabolic surveillance (glycemia and lipids) in NFAI despite ‘non-functioning’ DST results, and refine surgical criteria especially for patients with worsening metabolic profile or growth. Periodic re-evaluation for autonomous cortisol secretion is warranted.
Key Findings
- In non-surgical cohorts, diabetes risk increased (RR 1.33, 95% CI 1.07–1.65) and lipid disorders increased (RR 1.22, 95% CI 1.07–1.38) over follow-up.
- Surgery significantly improved hypertension (RR 0.67, 95% CI 0.52–0.86).
- During ~46 months, 4% (95% CI 2%–8%) enlarged >10 mm; 8% (95% CI 5%–14%) became functional during ~45 months.
- Findings suggest subtle hormone secretion may exist despite ‘non-functioning’ classification by 1 mg DST.
Methodological Strengths
- PRISMA-compliant meta-analysis pooling 18 studies across four major databases.
- Pre-specified DST threshold (≤50 nmol/L) to standardize inclusion and reduce misclassification.
Limitations
- Underlying studies were observational with potential heterogeneity and residual confounding.
- Limited randomized evidence; surgical selection biases may influence comparative outcomes.
Future Directions: Prospective cohorts and randomized trials to test refined diagnostic thresholds, surveillance intervals, and surgical criteria; development of more sensitive biomarkers for subtle cortisol autonomy.
BACKGROUND: Increased detection of non-functioning adrenal incidentalomas (NFAI) due to widespread abdominal imaging may underestimate associated metabolic risks. To examine NFAI's impact on metabolic comorbidities and evaluate outcomes in surgical and non-surgical management, including changes in NFAI characteristics during follow-up. METHODS: Meta-analysis of studies from PubMed, Embase, Cochrane Library, and Web of Science (January 2000 to May 2024). Studies focusing on patients with serum cortisol levels ≤ 50 nmol/L after 1 mg dexamethasone suppression test (DST). Prevalence of hypertension, diabetes, obesity, and lipid disorders before and after follow-up. Tumor growth (> 10 mm increase) and functional changes (1 mg DST retest) were assessed. RESULTS: Eighteen studies met inclusion criteria (n = 2,059). In the non-surgical group, diabetes (RR: 1.33, 95% CI: 1.07-1.65) and lipid disorders (RR: 1.22, 95% CI: 1.07-1.38) increased significantly, while hypertension (RR: 1.07, 95% CI: 0.99-1.16) and obesity (RR: 1.05, 95% CI: 0.91-1.21) showed no significant change. Surgical intervention significantly improved hypertension (RR: 0.67, 95% CI: 0.52-0.86). During mean follow-up of 46.1 months, 4% (95% CI: 2%- 8%) of NFAI enlarged > 10 mm, while 8% (95% CI: 5%- 14%) became functional during 45.1 months of follow-up. CONCLUSIONS: In patients with NFAI, subtle hormone secretion may exist despite current diagnostic criteria suggesting non-functionality. Such tumors show significant associations with metabolic disorders, particularly diabetes mellitus and dyslipidemia. Future research should focus on developing more sensitive diagnostic methods and establishing evidence-based surgical intervention criteria through prospective studies.